Convergent synthesis of hexameric naphthylene macrocycles with dicarboxylic imide appendages

Article abstract of DOI:10.1016/j.tetlet.2013.07.025

A series of macrocyclic compounds, [6]cyclo-2,7-naphthylenes ([6]CNAP), composed of six naphthylene units are synthesized through a [3+3] convergent route in good to moderate yields. The synthesis method allowed for the introduction of dicarboxylic imide moieties to the naphthylene units. Crystallographic analysis of a derivative possessing four imide groups showed a trimeric columnar assembly with an alignment of nanometer-sized macrocyclic pores.

Full text of DOI:10.1016/j.tetlet.2013.07.025

Tetrahedron Letters 54 (2013) 4963–4965
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Convergent synthesis of hexameric naphthylene macrocycles with
dicarboxylic imide appendages
⇑
Jing Yang Xue, Waka Nakanishi , Daiki Tanimoto, Daisuke Hara, Yuta Nakamura, Hiroyuki Isobe
Department of Chemistry and Advanced Institute for Materials Research (WPI-AIMR), Tohoku University, Aoba-ku, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of macrocyclic compounds, [6]cyclo-2,7-naphthylenes ([6]CNAP), composed of six naphthylene
units are synthesized through a [3+3] convergent route in good to moderate yields. The synthesis method
allowed for the introduction of dicarboxylic imide moieties to the naphthylene units. Crystallographic
analysis of a derivative possessing four imide groups showed a trimeric columnar assembly with an
alignment of nanometer-sized macrocyclic pores.
Received 28 May 2013
Revised 1 July 2013
Accepted 4 July 2013
Available online 11 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Convergent synthesis
Macrocycles
Polyaromatic hydrocarbons
p-Stack
Conjugated macrocycles are an interesting class of compounds,
not only because of the growing interest as organic materials but
also because of their discrete and -electron rich structures that
[6]CNAP derivatives. An interesting access to unique molecular
assembly has been observed to align 30-membered nanosized
rings in stacking macrocycles.
p
tolerate chemical modifications.1,2 The advent of powerful biaryl
coupling methods further facilitated the recent growth in the rep-
ertoires of arylene macrocyclic skeletons with direct aryl–aryl con-
nections, which provided interesting cyclic arrays of aromatic units
with sp2-networks. Unlike phenylene components for the arylene
macrocycles,3 however, naphthylene components have not been
exploited until recently, and only two types of cyclonaphthylenes
are so far available in the macrocycle repertoires. The first example
was planar cyclo-2,7-naphthylenes (CNAP),4 and the second exam-
ple was pseudo-tubular cyclo-1,4-naphthylene.5 The former
Departing from the one-pot, [1 Â 6] synthesis of unsubstituted
i0-[6]CNAP with a monomeric 2,7-dibromonaphthalene unit,4 we
developed a new convergent synthesis method with trimeric ter-
naphthyl units. The new method allowed us to synthesize a series
of in-[6]CNAP in good to moderate yields. We first synthesized the
fully functionalized naphthylene macrocyle. The coupling reaction
of dibrominated ternaphtyl 1 proceeded effectively with Ni com-
plex to afford 1,2,3,4,5,6-i6-[6]CNAP in 75% yield (Scheme 1). The
reaction was concise enough to be executed on a gram scale with
slightly lowered yield (62%).6
cyclonaphthylenes, especially hexameric [6]CNAP with 60
p
-elec-
The efficacy of the Ni-promoted convergent strategy depended
on the structures of the trimer, and we only detected a trace
amount of 1,2,4,5-i4-[6]CNAP from the Ni-promoted coupling of
the corresponding dibrominated ternaphthyl. We found, however,
that another stepwise coupling method using borylated ternaph-
thyl and PtCl2(cod) was applicable to this congener7,8 and obtained
1,2,4,5-i4-[6]CNAP in 33% yield from diborylated ternaphthyl 2 via
Pt-complex formation and subsequent reductive elimination. A
possible tetrameric intermediate comprising four Pt atoms and
twelve naphthyl units was not detected from this reaction, and
the absence is interesting in comparison with the Pt-mediated pro-
duction of tetramers with rigid arylenes.7 The Ni-promoted meth-
od was applicable to the synthesis of 1,4-i2-[6]CNAP, and we
obtained the compound in 24% yield from the [3+3] macrocycliza-
tion of dibromide 3. The notable efficiency of i6-[6]CNAP macrocyc-
lization is of mechanistic interest and should be further examined
in detail in due course.
trons, revealed unique properties of naphthylene macrocycles such
as bipolar charge transporting ability in organic light emitting de-
vices (OLED) and thermal stability reaching over 600 °C. Along
with these unique properties, the availability of various naphtha-
lene bases prompted us to explore the structural variations of
[6]CNAP, and we herein report the convergent synthesis of
[6]CNAP bearing dicarboxylic imide appendages (hereafter de-
noted as in-[6]CNAP where n represents the numbers of the imide
groups). Convergent [3+3] assembly with ternaphthyl units al-
lowed us to synthesize the representative congeners of new in-
⇑
Corresponding author. Fax: +81 22 795 6589.
E-mail address: isobe@m.tohoku.ac.jp (H. Isobe).
Present address: National Institute for Materials Science (NIMS), Tsukuba 305-
0044, Japan.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.025

4964
J. Y. Xue et al. / Tetrahedron Letters 54 (2013) 4963–4965
Figure 1. Structures of i0- and 1,2,4,5-i4-[6]CNAP from X-ray diffraction analysis.
Transparent orange planes represent the mean plane of the central 30-membered
ring. Color of atoms are as follows: Carbon = gray, hydrogen = white, nitro-
gen = blue, oxygen = red. (a) Molecular structure of i0-[6]CNAP. Angles show the
dihedral angles at the single-bond linkages. (b) Molecular structures of 1,2,4,5-i4-
[6]CNAP from Ref.4. Angles show the dihedral angles at the single-bond linkages. (c)
Packing structure of stacking trimer of 1,2,4,5-i4-[6]CNAP in space-filling models.
(d) Packing structure of 1,2,4,5-i4-[6]CNAP in space-filling models showing the
positions of neighboring trimers.
Scheme 1. [3+3] Convergent synthesis of in-[6]CNAP.
Table 1
Solubilities of in-[6]CNAP in CHCl3 at 25 °C
i6-[6]CNAP
i4-[6]CNAP
i2-[6]CNAP
i0-[6]CNAP
In M
In mg/L
7.6 Â 10À2
2.0 Â 10À3
1.5 Â 10À5
2.5 Â 10À6
1.6 Â 105
3.3 Â 103
19
2.0
orange.11 As shown in Figure 1a, the original i0-[6]CNAP possessed
an alternate arrangement of the dihedral angles at the single-bond
linkages, which resulted in the alternate orientations of the naph-
thylene units.4 The alternate orientation was maintained in the
molecules of i4-[6]CNAP at the top and the bottom of the trimeric
assembly, but the average dihedral angle was shrunk to ꢀ20° from
ꢀ30° of i0-[6]CNAP (Fig. 1b). The planarization was more profound
for the molecule in the middle of the trimer: The average dihedral
angle was 7°, and the alternate twist diminished.
Along with the deformation in the molecular structures, we
noted a stark difference in the packing structures of i4-[6]CNAP
and i0-[6]CNAP. The packing motif of the unsubstituted congener
was a ubiquitous herringbone type despite the unique macrocyclic
structure.4 On the other hand, the basic packing motif was a stack-
ing type for i4-[6]CNAP. Thus, the three molecules were assembled
in a stacking manner, and, as shown in Figure 1c, the mean planes
of the 30-membered rings were aligned parallel to each other. The
distance of the mean planes at the top and the bottom measured
6.82 Å, which showed the intimate van der Waals contact of the
macrocyclic molecules. The electrostatic complementarity be-
tween unsubstituted naphthylene units and imide-appended
naphthylene units may have played a key role for the stacking
assembly,12 and the central 30-membered rings of 0.9-nm diame-
ter were aligned to form a nanopore in the trimeric assembly. The
stacking, however, ended at the three layers, and the nanopore was
capped by the DIP groups of the neighboring trimers (Fig. 1d).13
The stacking is terminated, most likely because of the steric con-
gestions of the bulky groups at the peripheral of the macrocycle:
Twelve DIP groups in the stack left no space available for another
four DIP groups to intrude. Designing the multi-layered nanopor-
ous materials from the present macrocycles is of great interest,
We found that the convergent synthesis was also beneficial for
the isolation of the macrocycles. When we synthesized unsubsti-
tuted congener, i0-[6]CNAP, through the convergent route, the
compound was isolated in 19% yield. Although the yield was
slightly lower than that of the previous one-pot [1 Â 6] assembly
route (24%), the isolation of the compound was more cost-effective
for the convergent route. Thus, although the one-pot [1 Â 6]
assembly route required a large amount of expensive solvents for
the isolation, the convergent [3+3] route afforded the desired com-
pound simply through a single set of extraction of [9]CNAP with
DMF and a single recrystallization step from nitrobenzene.9
The introduction of imide groups with diisopropylphenyl (DIP)
moieties dramatically improved the solubility of the macrocycles.
Thus, the solubilities of in-[6]CNAP increased with the increase in
the numbers of the imide substituents to record 7.6 Â 10À2
,
2.0 Â 10À3, 1.5 Â 10À5, and 2.5 Â 10À6 M for n = 6, 4, 2, and 0 in
chloroform, respectively (Table 1). The improvement of the solubil-
ity is beneficial for the future development of the macrocycles that
severely suffered from the low solubility in the absence of the
imide appendages.4
Among the new macrocycles, we obtained a single crystal of
1,2,4,5-i4-[6]CNAP suitable for X-ray diffraction analysis and found
few structural features different from the unsubstituted conge-
ner.10 The recrystallization of this compound also reaped a benefit
from the improved solubility and did not require a peculiar anthra-
cene melt as the recrystallization solvent.4 The molecules formed a
unique trimeric assembly, and the structures are shown in Figure 1
with mean planes for the central 30-membered ring colored in

J. Y. Xue et al. / Tetrahedron Letters 54 (2013) 4963–4965
4965
for instance, through devising peripheral functional groups14 and
will be explored in due course. Preliminary investigations with
i2-[6]CNAP afforded needle-like crystals, which may indicate the
anisotropic crystal growth with i2-congeners with higher struc-
tural complementarity for stacking.
In summary, we have developed a convergent method for the
synthesis of a series of naphthylene macrocycles. As the conver-
gent method is versatile enough to accept cross-coupling reactions
for the final [3+3] assembly, further extensions will be reported in
due course. The possibility of columnar assembly of the macrocy-
3. (a) Rapson, W. S.; Shuttleworth, R. G.; van Niekerk, J. N. J. Chem. Soc. 1943, 326–
327; (b) Staab, H. A.; Binnig, F. Tetrahedron Lett. 1964, 5, 319–321; (c) Jasti, R.;
Bhattacharjee, J.; Neaton, J. B.; Bertozzi, C. R. J. Am. Chem. Soc. 2008, 130, 17646–
17647.
4. (a) Nakanishi, W.; Yoshioka, T.; Taka, H.; Xue, J. Y.; Kita, H.; Isobe, H. Angew.
Chem., Int. Ed. 2011, 50, 5323–5326; (b) Nakanishi, W.; Xue, J. Y.; Yoshioka, T.;
Isobe, H. Acta Crystallogr., Sect. E: Struct. Rep. Online 2011, E67, o1762–o1763.
5. Yagi, A.; Segawa, Y.; Itami, K. J. Am. Chem. Soc. 2012, 134, 2962–2965.
6. The scale-up synthesis forced us to utilize silica gel column chromatography
for the purification, which affected the recovery of materials and, hence,
resulted in the lower yield.
7. (a) Hitosugi, S.; Nakanishi, W.; Yamasaki, T.; Isobe, H. Nat. Commun. 2011, 2.
http://dx.doi.org/10.1038/ncomms1505; (b) Hitosugi, S.; Yamasaki, T.; Isobe, H.
J. Am. Chem. Soc. 2012, 134, 12442–12445; (c) Matsuno, T.; Kamata, S.; Hitosugi,
S.; Isobe, H. Chem. Sci. 2013. http://dx.doi.org/10.1039/c3sc50645b.
8. Yamago, S.; Watanabe, Y.; Iwamoto, T. Angew. Chem., Int. Ed. 2010, 49, 757–759.
9. The isolation of 1-g quantity of i0-[6]CNAP from [1 Â 6] synthesis required 19 L
of CHCl3 for removal of [7]CNAP, 10 L of 1-methylnaphthalene (ca. 270,000
yen) for the first recrystallization and 1 L of nitrobenzene for the second
recrystallization. On the other hand, based on the 200-mg scale synthesis
procedure, the isolation of 1-g quantity of i0-[6]CNAP from [3+3] convergent
synthesis should require 18 L of DMF for removal of [9]CNAP and 1 L of
nitrobenzene for the recrystallization.
10. CCDC928523 contains the supplementary crystallographic data for this letter.
These data can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
11. (a) Macrae, C. F.; Bruno, I. J.; Chisholm, J. A.; Edgington, P. R.; McCabe, P.;
Pidcock, E.; Rodriguez-Monge, L.; Taylor, R.; van de Streek, J.; Wood, P. A. J.
Appl. Cryst. 2008, 41, 466–470; (b) Macrae, C. F.; Edgington, P. R.; McCabe, P.;
Pidcock, E.; Shields, G. P.; Taylor, R.; Towler, M.; van de Streek, J. J. Appl. Cryst.
2006, 39, 453–457; (c) Bruno, I. J.; Cole, J. C.; Edgington, P. R.; Kessler, M. K.;
Macrae, C. F.; McCabe, P.; Pearson, J.; Taylor, R. Acta Cryst. 2002, B58, 389–397;
(d) Taylor, R.; Macrae, C. F. Acta Cryst. 2001, B57, 815–827.
12. Hunter, C. A.; Lawson, K. R.; Perkins, J.; Urch, C. J. J. Chem. Soc.,Perkin Trans. 2
2001, 651–669.
13. The unit cell contains 38 acetonitrile molecules, which have been treated as a
diffuse contribution to the overall scattering without specific atom positions by
SQUEEZE/PLATON. See Supplementary data for the details.
cles with a nanosized ring and 60p-electrons is an interesting sub-
ject to be explored by devising rational molecular designs in near
future.
Acknowledgments
This study is partly supported by KAKENHI (21685005,
20108015, 22550094) and NEDO. We thank Prof. T. Iwamoto (To-
hoku Univ.) for the X-ray instrument Prof. M. Kawano (POSTECH)
for preliminary X-ray analysis and T. Yoshioka for preliminary syn-
thetic investigations.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.07.
025.
References and notes
14. (a) Finke, A. D.; Gross, D. E.; Han, A.; Moore, J. S. J. Am. Chem. Soc. 2011, 133,
14063–14070; (b) Tashiro, S.; Kubota, R.; Shionoya, M. J. Am. Chem. Soc. 2012,
134, 2461–2464.
1. Iyoda, M.; Yamakawa, J.; Rahman, M. J. Angew. Chem., Int. Ed. 2011, 50, 10522–
10553.
2. Zang, L.; Che, Y.; Moore, J. S. Acc. Chem. Res. 2008, 10, 1596–1608.